Shandong Intervention Trial. In April, 2003, we completed the final endoscopies with gastric biopsies for an 8-year trial to determine if treatment for H. pylori, supplementation with garlic extract, or supplementation with a mixture of vitamins E, C, and selenium can reduce the prevalence of severe precancerous gastric lesions. The trial will also provide an evaluation of therapy for H. pylori, including an assessment of reinfection rates. 3411 adults aged 35-70 from 13 villages in Linqu County, Shandong Province, are participating in the trial. To evaluate the effectiveness of the Calijing disinfection kit (an endoscope disinfection method used in about 1500 hospitals in China) in eradicating H. pylori, bacteriologic studies were conducted at Veterans Affairs Medical Center, Houston, TX on endoscopes and forceps from 49 H. pylori postive patients. Before dis-infection, at least one endoscope culture site was H. pylori positive in 39/49 (79.6%) specimens, whereas H. pylori was not isolated from any endoscopic culture site post-disinfection. However, non-H. pylori bacteria and fungi were recoved from 22.6% of the post-disinfection cultures. Breast Cancer Detection Demonstration Project Follow-up Study This study follows about 60,000 women who were former participants in the Breast Cancer Detection Demonstration Project (BCDDP). During the past year the following analyses have been completed: 1) hormone replacement therapy and risk of ovarian cancer; 2) family history of breast cancer as a determinant of risk of developing endometrial cancer; 3) family history of breast cancer as a determinant of risk of developing ovarian cancer; 4) medication use and risk of ovarian cancer; 5) physical activity and the risk of endometrial cancer; 6) physical activity and risk of ovarian cancer; 7) meat, dietary fat and risk of colorectal cancer; 8) folate, methionine, alcohol, and risk of colorectal cancer; 9) dietary fiber and risk of colorectal cancer;10) diet quality and subsequent cancer incidence and mortality, and 11) calcium and colorectal cancer. Breast Cancer Serum Bank Study (Study ID 193) The Breast Cancer Serum Bank Study is a case-control study involving post-menopausal patients who provided serum prior to breast biopsy or mastectomy in three hospitals in Grand Rapids, Michigan, between 1977-1987. Two case groups, 185 subjects with localized breast cancer and 186 subjects with benign epithelial hyperplasia of the breast, were compared to 159 subjects with non-proliferative breast conditions that have not been associated with increased breast cancer risk. We found the following: 1) no associations between IGF-I and IGFBP-3 and either breast cancer or benign hyperplasia; 2) significant positive associations between c-peptide and risk of benign hyperplasia, but not risk of breast cancer, and; 3) positive associations between estrogens, but not androgens, and risk of breast cancer and benign hyperplasia. Breast Cancer Risk Assessment We have modeled the risk of developing breast cancer using factors such as a positive family history. We adapted the risk model to aid in counseling women on the risks and benefits of tamoxifen. We used this risk/benefit analysis and data from the 2000 National Health Interview Survey to estimate that 15.57% of white women would be eligible to receive tamoxifen according to FDA criteria, but only 4.9% would have a positive risk benefit ratio. It is mainly young women with a high risk of breast cancer or somewhat older women with elevated breast cancer risk who have no uterus who stand to benefit. We are exploring the feasibility of improving the model by incorporating information on mammographic density and by using genetic information. We completed work on the reliability of mammographic density measurements and found correlations above 0.9 in repeated measurements of the same films at different times. Analyses are underway to incorporate mammographic density into models for projecting absolute risk. The models were also used to determine whether geographic variation in breast cancer rates can be explained by regional differences in the prevalence of known risk factors. Inflammatory Breast Cancer (IBC) Study We designed a 5 year case-control study of inflammatory breast cancer. The proposed study will include all IBC cases (n = 300) and a sample of 300 breast cancer cases with no signs characteristic of IBC identified at the National Cancer Institute-Cairo and the Institut Salah Azaiz in Tunisia. 450 hospital controls from affiliated general hospitals will also be included. In addition to questionnaires, measurements of height, weight, waist, and hip, and the collection of blood from all study subjects, digitial photographs will be taken of the breasts of all IBC cases. Pre-treatment frozen tumor tissue will be obtained from IBC and non-IBC cases. The study aims :1) to examine the epidemiology of IBC and non-IBC breast cancer; and 2) to detect gene and protein expression differences between IBC versus non-IBC tumor tissue. We prepared a protocol, forms, and detailed procedures and held a collaborators? meeting in Bethesda in March 2003. Melanoma Risk Assessment We modeled the absolute risk of cutaneous invasive melanoma based on an individual?s skin complexion, sunburn characteristics, degree of freckling and solar damage on the back, and the presence of nevi on the back. The primary care provider can use these simple risk factors to identify individuals at high risk and send them for examination by an expert. Shandong Polymorphism Study We looked for associations between each of eight candidate polymorphisms (CYP2E1, CYP2A6, GSTT1, GSTP1, GSTM1, ALDH2, ODC and AGT) with advanced precancerous gastric lesions in 908 subjects selected from 2625 subjects who had endoscopies with biopsies in 1989 in Linqu County, Shandong Province. Preliminary analyses revealed no statistically significant evidence of a main effect for any of these loci under additive, recessive or dominant genetic models. Linxian Follow-up Study Two large, nutrition intervention trials were conducted in Linxian China between 1985-1991. These trials tested the effect of multiple vitamins and minerals in the prevention of esophageal cancer in a population with the highest known rate for this disease in the world. Results from the trials showed that beta carotene + vitamin E + selenium reduced total mortality, total cancer mortality, and stomach cancer incidence and mortality. Multivitamins/minerals also showed reduction in pre-malignant lesions. Using baseline sera and data from continued follow-up of this cohort, we determined associations of baseline serum selenium, beta-carotene and vitamin E with esophageal squamous cell carcinoma (ESSC) and with gastric cardia cancer (GCC). Selenium and vitamin E were independent risk factors for ESSC and GCC, but there was no association with beta-carotene. Long-term follow-up showed that the protective effect of treatment with beta carotene + vitamin E + selenium persisted over 15 years. Using data from Linxian, we completed two DNA polymorphism studies. We found that individuals homozygous for the variant MTHFR C677T allele have higher risks of ESSC /GCA; and those with any variant MTRR A66G allele have increased risk of ESSC. In a study of Interleukin 8 polymorphisms and its receptor, we found increased GCC risk associated with two variant alleles, and a specific haplotype containing both those variants.